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<p>Intracellular organelles are pivotal for maintaining cellular homeostasis, with lipids serving as key mediators of inter-organellar contact and communication. However, the limited understanding of lipid chemical diversity and composition has constrained research into lipid-mediated organellar functions. The A549 cell lines, a widely used human non-small cell lung cancer model in both basic research and drug discovery, provide an ideal system for investigations. In this study, we generated the quantitative lipidomic atlas covering seven subcellular compartments, including mitochondria, ER, Golgi apparatus, nucleus, exosome, lysosome and plasma membrane in A549 cells. This atlas encompasses appropriately 1,400 lipid species across 40 subclasses and systematically characterizes the proportional composition and distinct features of each organelle. We analyzed the key features, including lipid species distribution, unsaturation and chain length patterns, as well as the ratios of polyunsaturated fatty acids to monounsaturated and saturated fatty acids (PUFA:MUFA+SFA) and cylindrical to non-cylindrical lipids. Causal connection and pair-by-pair correlation analyses revealed that the ER acts as the primary source of lipid flow, with mitochondria as its terminal. Specifically, glycosylceramide and dihexosylceramides (Hex2Cer) emerge as central hubs exhibiting significant correlations with other lipids across the seven subcellular lipidomes. Taken together, this study establishes a reference lipidome for seven major organelles, maps their distinct lipidomic characteristics and the correlations of lipid-mediated interorganelles, and provides new insights into the lipid-based communication networks in cancer cells.</p>

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The lipidomic atlas for cellular organelles to reveal the central role of mitochondria in organelle communication

  • 期刊论文

  • 发表日期：

    2026年5月7日

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  • Wenjuan Qian,
  • Qinsheng Chen,
  • Haoran Hu,
  • Shuaiyao Wang,
  • Hongyan Yao,
  • Huiru Tang

摘要

Intracellular organelles are pivotal for maintaining cellular homeostasis, with lipids serving as key mediators of inter-organellar contact and communication. However, the limited understanding of lipid chemical diversity and composition has constrained research into lipid-mediated organellar functions. The A549 cell lines, a widely used human non-small cell lung cancer model in both basic research and drug discovery, provide an ideal system for investigations. In this study, we generated the quantitative lipidomic atlas covering seven subcellular compartments, including mitochondria, ER, Golgi apparatus, nucleus, exosome, lysosome and plasma membrane in A549 cells. This atlas encompasses appropriately 1,400 lipid species across 40 subclasses and systematically characterizes the proportional composition and distinct features of each organelle. We analyzed the key features, including lipid species distribution, unsaturation and chain length patterns, as well as the ratios of polyunsaturated fatty acids to monounsaturated and saturated fatty acids (PUFA:MUFA+SFA) and cylindrical to non-cylindrical lipids. Causal connection and pair-by-pair correlation analyses revealed that the ER acts as the primary source of lipid flow, with mitochondria as its terminal. Specifically, glycosylceramide and dihexosylceramides (Hex2Cer) emerge as central hubs exhibiting significant correlations with other lipids across the seven subcellular lipidomes. Taken together, this study establishes a reference lipidome for seven major organelles, maps their distinct lipidomic characteristics and the correlations of lipid-mediated interorganelles, and provides new insights into the lipid-based communication networks in cancer cells.